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Vitamin A-modified ZIF-8 lipid nanoparticles for the therapy of liver fibrosis

journal contribution
posted on 2024-01-22, 03:33 authored by Alex QinAlex Qin, Xuening Du, Kaili Wang, Da Wang, Jiani Zheng, Haiyan Xu, Xiuyan Wei, Yue Yuan
Liver fibrosis (LF) is one of the major diseases that threaten human health. Until now, no effective drugs have been approved for clinical anti-liver fibrosis treatment. In this study, zeolitic imidazolate framework-8 (ZIF-8) lipid nanoparticles loaded with pirfenidone (PFD) and modified with vitamin A (VA) were constructed (VA-PFD@ZIF-8@DMPC NPs). PFD was embedded in ZIF-8 by the "one-pot" method, and the prepared ZIF-8 had a small particle size (84.3 nm) and high drug loading (54.46%). Moreover, the inherent pH sensitivity of ZIF-8 makes it stable in a normal physiological environment and collapsed in an acidic environment, thus controlling drug release and preventing drug leakage. Besides, the phospholipid layer makes the nano-drug delivery system dispersible and improves its biocompatibility. More importantly, VA is modified on the surface of nanoparticles (NPs), which can target the highly expressed retinol-binding protein receptor (RBPR) on the surface of hepatic stellate cells (HSCs), thereby accurately increasing the local drug concentration at the site of LF. In vivo experiments showed that VA-PFD@ZIF-8@DMPC NPs can reduce liver injury, improve the degree of LF, and exert specific therapeutic effects on LF. In conclusion, this nano-delivery system may become a novel and effective anti-liver fibrosis treatment.

History

Journal

INTERNATIONAL JOURNAL OF PHARMACEUTICS

Volume

642

Article number

ARTN 123167

Location

Netherlands

ISSN

0378-5173

eISSN

1873-3476

Language

English

Publisher

ELSEVIER